Xu Jinjing, Ji Hongyan, Yao Ying, Liu Xudong, Huang Yutao, Zhang Yanqing, Tang Yaqin, Chen Jing
Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, 225001, Jiangsu, China.
Institute of Clinical Pharmacology, General Hospital of Ningxia Medical University, Ningxia, 750004, China.
Sci Rep. 2025 Apr 21;15(1):13701. doi: 10.1038/s41598-025-98409-x.
Chrysosplenetin, a polymethoxy flavonol purified in our laboratory from the waste products generated during the industrial extraction of artemisinin, has been previously demonstrated to be a potential inhibitor of artemisinin resistance. Based on NMR-untargeted metabolomics, one of its hypothesized mechanisms of action is associated with the regulation of amino acid metabolism. In this study, we further quantified the key amino acids using LC-MS/MS targeted metabolomics and screened out the perturbed metabolic pathway network, which was characterized by tissue-specific differences. As a result, among the commonly and uniquely altered metabolites, increased levels of phenylalanine, tryptophan, and isoleucine were detected in the serum and various organs of the resistant groups. Interestingly, while the individual use of chrysosplenetin or artemisinin elevated the contents of these amino acids, their combination led to a significant down-regulation of these amino acids in the serum and intestines. Therefore, chrysosplenetin has the potential to act as a restorer of amino acid metabolism homeostasis, which is associated with artemisinin resistance in Plasmodium berghei K173.
金缕梅素是我们实验室从青蒿素工业提取过程中产生的废弃物中纯化得到的一种多甲氧基黄酮醇，此前已被证明是青蒿素抗性的潜在抑制剂。基于核磁共振非靶向代谢组学，其一种假设的作用机制与氨基酸代谢的调节有关。在本研究中，我们使用液相色谱-串联质谱靶向代谢组学进一步定量了关键氨基酸，并筛选出了以组织特异性差异为特征的受干扰代谢途径网络。结果，在常见和独特改变的代谢物中，在抗性组的血清和各种器官中检测到苯丙氨酸、色氨酸和异亮氨酸水平升高。有趣的是，虽然单独使用金缕梅素或青蒿素会提高这些氨基酸的含量，但它们的组合导致血清和肠道中这些氨基酸显著下调。因此，金缕梅素有可能作为氨基酸代谢稳态的恢复剂，这与伯氏疟原虫K173中的青蒿素抗性有关。
